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1.
J Allergy Clin Immunol ; 144(6): 1542-1550.e1, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31536730

RESUMO

BACKGROUND: Although the different age groups had differences in sensitivity of asthma exacerbations (AEs) to environmental factors, no comprehensive study has examined the age-stratified effects of environmental factors on AEs. OBJECTIVE: We sought to examine the short-term effects in age-stratified groups (infants, preschool children, school-aged children, adults, and the elderly) of outdoor environmental factors (air pollutants, weather conditions, aeroallergens, and respiratory viral epidemics) on AEs. METHODS: We performed an age-stratified analysis of the short-term effects of 4 groups of outdoor environmental factors on AEs in Seoul Metropolitan City (Korea) from 2008 and 2012. The statistical analysis used a Poisson generalized linear regression model, with a distributed lag nonlinear model for identification of lagged and nonlinear effects and convergent cross-mapping for identification of causal associations. RESULTS: Analysis of the total population (n = 10,233,519) indicated there were 28,824 AE events requiring admission to an emergency department during the study period. Diurnal temperature range had significant effects in pediatric (infants, preschool children, and school-aged children) and elderly (relative risk [RR], 1.056-1.078 and 1.016, respectively) subjects. Tree and weed pollen, human rhinovirus, and influenza virus had significant effects in school-aged children (RR, 1.014, 1.040, 1.042, and 1.038, respectively). Tree pollen and influenza virus had significant effects in adults (RR, 1.026 and 1.044, respectively). Outdoor air pollutants (particulate matter of ≤10 µm in diameter, nitrogen dioxide, ozone, carbon monoxide, and sulfur dioxide) had significant short-term effects in all age groups (except for carbon monoxide and sulfur dioxide in infants). CONCLUSION: These findings provide a need for the development of tailored strategies to prevent AE events in different age groups.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma , Exposição Ambiental/efeitos adversos , Modelos Biológicos , Sistema de Registros , Adolescente , Adulto , Fatores Etários , Asma/epidemiologia , Asma/etiologia , Criança , Feminino , Humanos , Masculino , República da Coreia/epidemiologia , Fatores de Risco
2.
J Asthma ; 55(12): 1343-1351, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29300537

RESUMO

OBJECTIVE: Bronchodilator responses (BDRs) from impulse oscillometry (IOS) are not interchangeable with those from spirometry. We aimed to identify the characteristics of children with small airway hyperresponsiveness and to determine whether BDR from IOS provides an important supplement to BDR from spirometry. METHODS: The records of 592 children with asthma or suspected asthma who underwent spirometric and oscillometric BDRs were retrospectively reviewed. Oscillometric BDR was defined as positive when relative or absolute changes of Rrs5 or Xrs5 were beyond two standard deviations and spirometric BDR as positive when absolute change of forced expiratory volume in one second (FEV1) was ≥12%. Subjects were classified as positive for spirometric BDR only, positive for oscillometric BDR only, positive for both BDRs, or negative for both BDRs. RESULTS: The results indicated that 101 (17.6%) subjects were positive for spirometric BDR only, 49 (8.5%) positive for oscillometric BDR only, 48 (8.3%) positive for both BDRs, and 377 (65.6%) negative for both BDRs. The agreement between spirometric and oscillometric BDRs was poor. Baseline FEV1, Rrs5, and Xrs5 values strongly influenced the BDRs. Subjects positive for oscillometric BDR only were found to be younger than those positive for spirometric BDR only (P < 0.001). Subjects positive for both BDRs were more likely to have asthma, atopic dermatitis, wheezing apart from cold, or decreased baseline lung function relative to those positive in either test (P < 0.001). CONCLUSIONS: There was a low concordance between spirometric and oscillometric BDRs. Use of IOS to detect small airway hyperresponsiveness may add more information about a clinical profile of subjects with asthma.


Assuntos
Asma/fisiopatologia , Oscilometria/métodos , Hipersensibilidade Respiratória/fisiopatologia , Espirometria/métodos , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Testes de Função Respiratória , Estudos Retrospectivos
3.
Int Arch Allergy Immunol ; 174(3-4): 183-189, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29130983

RESUMO

OBJECTIVE: The prevalence of local allergic rhinitis (LAR) in nonatopic children remains unknown. This study aimed to determine the prevalence, clinical characteristics, and severity of LAR in children in comparison to classical allergic rhinitis (AR) and nonallergic rhinitis (NAR). STUDY DESIGN: A total of 145 children (aged 1-18 years) were enrolled and classified into 3 groups (AR, NAR, and LAR) based on a skin prick test (SPT) and a nasal provocation test (NPT) with house dust mite, i.e., Dermatophagoides pteronyssinus. NPT positivity was defined as a symptom score ≥2 standard deviations (SDs) above the healthy control score. RESULTS: Eighty-one children had AR (55.9%), and 64 (44.1%) had symptoms of rhinitis with negative SPT; 59 NAR (40.7%) and 5 LAR (3.4%) children were identified. The κ score for agreement between the SPT and the NPT results was 0.778 (95% CI 0.726-0.830, p < 0.001). A significant correlation was observed between wheal diameter and maximum nasal symptom score provoked by D.pteronyssinus (rho = 0.589, p < 0.001). Nasal severity according to the ARIA guideline did not show any differences in the 3 groups (p = 0.693). The AR group was older than the LAR and NAR groups (AR > LAR > NAR, p = 0.003). CONCLUSIONS: Despite the evidence to support the existence of LAR in pediatric populations, we found that its prevalence was relatively low, possibly due to the high rate of agreement between SPT and NPT. Further investigations are needed to identify immunological as well as clinical implications of LAR.


Assuntos
Hipersensibilidade/epidemiologia , Rinite Alérgica/epidemiologia , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Imunização , Lactente , Coreia (Geográfico)/epidemiologia , Masculino , Gravidez , Prevalência , Pyroglyphidae , Rinite Alérgica/imunologia , Testes Cutâneos
4.
Biogerontology ; 15(2): 153-64, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24337961

RESUMO

Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 µg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Drosophila melanogaster/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Viscum album/química , Animais , Restrição Calórica , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Expressão Gênica/efeitos dos fármacos , Genes de Insetos , Histona Desacetilases/genética , Masculino , Medicina Tradicional Coreana , Extratos Vegetais/farmacologia , Sirtuínas/genética , Estresse Fisiológico/efeitos dos fármacos
5.
Exp Cell Res ; 318(5): 670-81, 2012 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-22265916

RESUMO

Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis.


Assuntos
Drosophila melanogaster/enzimologia , Homeostase , Intestinos/enzimologia , Metaloproteinase 1 da Matriz/metabolismo , Animais , Proliferação de Células , Enterócitos/enzimologia , Receptores ErbB/metabolismo , Técnicas de Silenciamento de Genes , Hiperplasia/enzimologia , Intestinos/patologia , Intestinos/fisiopatologia , Expectativa de Vida , Metaloproteinase 1 da Matriz/deficiência , Metaloproteinase 1 da Matriz/genética , Índice Mitótico , Estresse Oxidativo , Interferência de RNA , Nicho de Células-Tronco , Células-Tronco/enzimologia , Células-Tronco/patologia
6.
Insects ; 13(2)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35206792

RESUMO

BACKGROUND: Commensal microbiota live in their host with a symbiotic relationship that affects the host's health and physiology. Many studies showed that microbial load and composition were changed by aging and observed that increasing the abundance and changing the composition of commensal microbes had detrimental effects on host lifespan. We hypothesized that dysbiosis of the intestinal microbiota leads to systemic effects in aging flies as a result of the increased intestinal permeability. METHODS: We used the fruit fly, Drosophila melanogaster, laboratory strains w1118, as a model system with many advantages for microbe-host studies. RESULTS: The incidence of intestinal dysfunction was increased with age, and intestinal dysfunction increased the permeability of the fly intestine to resident microbes. The lifespan of flies with an intestinal barrier dysfunction was increased by removal of the microbes. Interestingly, some bacteria were also found in the hemolymph of flies with intestinal barrier dysfunction. CONCLUSION: Our findings suggest the possibility that, as the host ages, there is an increase in intestinal permeability, which leads to an increased intestinal microbial load and a reduction in the host lifespan. Our data therefore indicate a connection between commensal microbes and host lifespan.

7.
Diabetes Metab J ; 46(1): 15-37, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34965646

RESUMO

Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Músculo Esquelético/patologia
8.
Metabolism ; 129: 155139, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35063533

RESUMO

OBJECTIVE: Maintaining a constant core body temperature is essential to homeothermic vertebrate survival. Adaptive thermogenesis in brown adipose tissue and skeletal muscle is the primary mechanism of adjustment to an external stimulus such as cold exposure. Recently, several reports have revealed that the liver can play a role as a metabolic hub during adaptive thermogenesis. In this study, we suggest that the liver plays a novel role in secreting thermogenic factors in adaptive thermogenesis. Bone morphogenetic protein 9 (BMP9) is a hepatokine that regulates many biological processes, including osteogenesis, chondrogenesis, hematopoiesis, and angiogenesis. Previously, BMP9 was suggested to affect preadipocyte proliferation and differentiation. However, the conditions and mechanisms underlying hepatic expression and secretion and adipose tissue browning of BMP9 remain largely unknown. In this study, we investigated the physiological conditions for secretion and the regulatory mechanism of hepatic Bmp9 expression and the molecular mechanism by which BMP9 induces thermogenic gene program activation in adipose tissue. Here, we also present the pharmacological effects of BMP9 on a high-fat-induced obese mouse model. METHODS: To investigate the adaptive thermogenic role of BMP9 in vivo, we challenged mice with cold temperature exposure for 3 weeks and then examined the BMP9 plasma concentration and hepatic expression level. The cellular mechanism of hepatic Bmp9 expression under cold exposure was explored through promoter analysis. To identify the role of BMP9 in the differentiation of brown and beige adipocytes, we treated pluripotent stem cells and inguinal white adipose tissue (iWAT)-derived stromal-vascular (SV) cells with BMP9, and brown adipogenesis was monitored by examining thermogenic gene expression and signaling pathways. Furthermore, to evaluate the effect of BMP9 on diet-induced obesity, changes in body composition and glucose tolerance were analyzed in mice administered recombinant BMP9 (rBMP9) for 8 weeks. RESULTS: Hepatic Bmp9 expression and plasma levels in mice were significantly increased after 3 weeks of cold exposure. Bmp9 mRNA expression in the liver was regulated by transcriptional activation induced by cAMP response-element binding protein (CREB) and CREB-binding protein (CBP) on the Bmp9 promoter. Treatment with BMP9 promoted the differentiation of multipotent stem cells and iWAT-derived SV cells into beige adipocytes, as indicated by the increased expression of brown adipocyte and mitochondrial biogenesis markers. Notably, activation of the mothers against decapentaplegic homolog 1 (Smad1) and p44/p42 mitogen-activated protein kinase (MAPK) pathways was required for the induction of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) expression in BMP9-induced differentiation of SVs into beige adipocytes. The administration of rBMP9 in vivo also induced browning markers in white adipose tissue. In high-fat diet-induced obese mice, rBMP9 administration conferred protection against obesity and enhanced glucose tolerance. CONCLUSIONS: BMP9 is a hepatokine regulated by cold-activated CREB and CBP and enhances glucose and fat metabolism by promoting the activation of the thermogenic gene program in adipocytes. These data implicate BMP9 as a potential pharmacological tool for protecting against obesity and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Fator 2 de Diferenciação de Crescimento/metabolismo , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Temperatura Baixa , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Fator 2 de Diferenciação de Crescimento/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Termogênese/genética , Proteína Desacopladora 1/metabolismo
9.
Cell Struct Funct ; 36(2): 197-208, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21979236

RESUMO

Recent studies have suggested the involvement of epigenetic factors such as methyl-CpG-binding protein-2 (MeCP2) in tumorigenesis. In addition, cancer may represent a stem cell-based disease, suggesting that understanding of stem cell regulation could provide valuable insights into the mechanisms of tumorigenesis. However, the function of epigenetic factors in stem cell regulation in adult tissues remains poorly understood. In the present study, we investigated the role of human MeCP2 (hMeCP2), a bridge factor linked to DNA modification and histone modification, in stem cell proliferation using adult Drosophila midgut, which appears to be an excellent model system to study stem cell biology. Results show that enterocyte (EC)-specific expression of hMeCP2 in adult midgut using an exogenous GAL4/UAS expression system induced intestinal stem cell (ISC) proliferation marked by staining with anti-phospho-histone H3 antibody and BrdU incorporation assays. In addition, hMeCP2 expression in ECs activated extracellular stress-response kinase signals in ISCs. Furthermore, expression of hMeCP2 modulated the distribution of heterochromatin protein-1 in ECs. Our data suggests the hypothesis that the expression of hMeCP2 in differentiated ECs stimulates ISC proliferation, implying a role of MeCP2 as a stem cell regulator.


Assuntos
Intestinos/citologia , Proteína 2 de Ligação a Metil-CpG/metabolismo , Células-Tronco/citologia , Animais , Bromodesoxiuridina/metabolismo , Proliferação de Células , Células Cultivadas , Cromatina/metabolismo , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Drosophila , Proteínas de Drosophila/metabolismo , Histonas/metabolismo , Humanos , Proteína 2 de Ligação a Metil-CpG/genética , Células-Tronco/metabolismo , Transfecção
10.
Biochim Biophys Acta ; 1799(7): 510-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20346429

RESUMO

The Drosophila midgut is an excellent model for evaluation of gene networks that regulate adult stem cell proliferation and differentiation. The Drosophila p38b (D-p38b) gene has been shown to be involved in intestinal stem cell (ISC) proliferation and differentiation in the adult midgut. Here, we report that D-p38b gene expression is regulated by DREF (DNA replication-related element binding factor) in the adult midgut. We have identified a DRE in the 5'-flanking region of the D-p38b gene and showed that DREF could bind to this DRE via a gel mobility shift assay and a ChIP assay. Base-substitution mutations of the D-p38b promoter DRE and analyses of transformants carrying D-p38b-lacZ or D-p38b-DREmut-lacZ indicated that this DRE is required for the activity of the D-p38b gene promoter. Furthermore, by using the GAL4-UAS system, we showed that DREF regulates the activity of the D-p38b gene promoter in adult ISCs and progenitors. In addition, the D-p38b knockdown phenotypes in the midgut were rescued by DREF overexpression, suggesting a functional link between these two factors. Our results suggest that the D-p38b gene is regulated by the DREF pathway and that DREF is involved in the regulation of proliferation and differentiation of Drosophila ISCs and progenitors.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Mucosa Intestinal/metabolismo , Proteína Quinase 11 Ativada por Mitógeno/genética , Proteína Quinase 11 Ativada por Mitógeno/metabolismo , Fatores de Transcrição/genética , Animais , Animais Geneticamente Modificados , Linhagem da Célula , Proteínas de Drosophila/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Modelos Biológicos , Mutação , Fenótipo , Regiões Promotoras Genéticas , Células-Tronco/citologia , Fatores de Transcrição/metabolismo
11.
Geriatr Gerontol Int ; 21(8): 725-731, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34101322

RESUMO

AIM: We examined the underlying mechanisms associated with the longevity effects of Korean mistletoe extract (KME) in Drosophila melanogaster. METHODS: We measured the lifespan of sirtuin, chico and foxo mutant flies fed KME, the expression of the forkhead box O (FOXO) target genes and insulin-like peptide genes, and the localization of FOXO in flies fed the KME. RESULTS: The longevity effect of KME was abolished in sirtuin, chico and foxo null mutant flies. In addition, the expression of FOXO target genes and the localization of FOXO into nuclei were increased in flies fed KME, but the expression of the insulin-like peptide genes was decreased by KME supplementation. CONCLUSIONS: The results show that KME extends the fly lifespan through sirtuin-induced FOXO activation. We suggest that KME has potential use as a beneficial anti-aging and longevity supplement. Geriatr Gerontol Int 2021; 21: 725-731.


Assuntos
Proteínas de Drosophila , Erva-de-Passarinho , Viscum album , Viscum , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Fatores de Transcrição Forkhead/genética , Longevidade , República da Coreia
12.
Microorganisms ; 9(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374132

RESUMO

Ionizing radiation induces biological/physiological changes and affects commensal microbes, but few studies have examined the relationship between the physiological changes induced by irradiation and commensal microbes. This study investigated the role of commensal microbes in the γ-ray irradiation-induced physiological changes in Drosophila melanogaster. The bacterial load was increased in 5 Gy irradiated flies, but irradiation decreased the number of operational taxonomic units. The mean lifespan of conventional flies showed no significant change by irradiation, whereas that of axenic flies was negatively correlated with the radiation dose. γ-Ray irradiation did not change the average number of eggs in both conventional and axenic flies. Locomotion of conventional flies was decreased after 5 Gy radiation exposure, whereas no significant change in locomotion activity was detected in axenic flies after irradiation. γ-Ray irradiation increased the generation of reactive oxygen species in both conventional and axenic flies, but the increase was higher in axenic flies. Similarly, the amounts of mitochondria were increased in irradiated axenic flies but not in conventional flies. These results suggest that axenic flies are more sensitive in their mitochondrial responses to radiation than conventional flies, and increased sensitivity leads to a reduced lifespan and other physiological changes in axenic flies.

13.
Pediatr Pulmonol ; 55(12): 3279-3286, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32965787

RESUMO

BACKGROUND: To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. METHODS: Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. RESULTS: Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. CONCLUSION: In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.


Assuntos
Acetatos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Ciclopropanos/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Quinolinas/administração & dosagem , Sulfetos/administração & dosagem , Administração por Inalação , Albuterol/administração & dosagem , Asma/metabolismo , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Criança , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Óxido Nítrico/metabolismo , Espirometria , Suspensão de Tratamento
14.
Adv Biosyst ; 4(7): e1900248, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32558394

RESUMO

Many studies utilizing animal models have revealed the genetic and pharmacogenetic modulators of the rate of organismal aging. However, finding routes for healthy aging during extended life remains one of the largest questions. With regards to an antiaging reagent, it has been shown that natural phytochemical syringaresinol (SYR) delays cellular senescence by activating sirtuin1 (SIRT1). Here, it is found that SYR treatment results in metabolic changes similar to those observed during dietary restriction (DR). The DR mimetic effects are mediated by FoxO3a-dependent SIRT1 activation and insulin/insuline growth factor-1 signaling modulation. The direct binding of SYR-FoxO3a is identified and this could partially explain the DR-like phenotype. The report gives a clue as to how the longevity gene involves the DR pathway and suggests that natural phytochemicals applied as a geroprotector mimics DR effects.


Assuntos
Materiais Biomiméticos/farmacologia , Restrição Calórica , Proteína Forkhead Box O3/metabolismo , Compostos Fitoquímicos/farmacologia , Animais , Reprogramação Celular , Camundongos , Sirtuína 1/metabolismo
15.
Biochim Biophys Acta ; 1779(12): 789-96, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18760387

RESUMO

Drosophila big brain (bib) encodes for a protein similar to members of the major intrinsic protein family, which includes the water- and ion-conducting aquaporin (AQP) channels. In mammals, AQP dysregulation has been implicated in a variety of diseases, including colorectal cancer and colonic injury. However, the regulatory mechanisms of AQP expression remain to be clearly elucidated. In this study, as we found a DREF binding site (DRE) in the 5'-flanking regions of both the Drosophila bib gene and the human AQP1 gene, we assessed the role of DREF in bib gene expression. DREF in Drosophila and humans has been demonstrated to function as a key transcriptional activator for cell proliferation-related genes. Herein, we demonstrate that the DRE is required for optimal promoter activity of Drosophila bib gene, particularly in the larval imaginal discs, which are actively proliferating tissues, as well as the adult hindgut. Our results may provide insight into the mechanisms inherent to the regulation of mammalian AQP genes.


Assuntos
Aquaporinas/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Fatores de Transcrição/fisiologia , Animais , Animais Geneticamente Modificados , Aquaporina 1/metabolismo , Núcleo Celular/metabolismo , Drosophila melanogaster , Regulação da Expressão Gênica , Humanos , Íons , Modelos Biológicos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Água/química
16.
BMB Rep ; 52(1): 24-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30526767

RESUMO

Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide. [BMB Reports 2019; 52(1): 24-34].


Assuntos
Envelhecimento/fisiologia , Senescência Celular/fisiologia , Sirtuína 1/fisiologia , Animais , Restrição Calórica , Dano ao DNA , Reparo do DNA/fisiologia , Humanos , Longevidade , Resveratrol , Transdução de Sinais/fisiologia , Sirtuína 1/metabolismo , Telômero
17.
Aging (Albany NY) ; 11(13): 4611-4640, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299010

RESUMO

Commensal microbes have mutualistic relationships with their host and mainly live in the host intestine. There are many studies on the relationships between commensal microbes and host physiology. However, there are inconsistent results on the effects of commensal microbes on host lifespan. To clarify this controversy, we generated axenic flies by using two controlled methods - bleaching and antibiotic treatment - and investigated the relationship between the commensal microbes and host lifespan in Drosophila melanogaster. The removal of microbes by using bleaching and antibiotic treatments without detrimental effects increased fly lifespan. Furthermore, a strain of flies colonized with a high load of microbiota showed a greater effect on lifespan extension when the microbes were eliminated, suggesting that commensal bacteria abundance may be a critical determinant of host lifespan. Consistent with those observations, microbial flora of aged fly gut significantly decreased axenic fly lifespan via an increase in bacterial load rather than through a change of bacterial composition. Our elaborately controlled experiments showed that the elimination of commensal microbes without detrimental side effects increased fly lifespan, and that bacterial load was a significant determinant of lifespan. Furthermore, our results indicate the presence of a deterministic connection between commensal microbes and host lifespan.


Assuntos
Drosophila melanogaster/microbiologia , Microbioma Gastrointestinal , Longevidade , Fatores Etários , Animais , Carga Bacteriana , Drosophila melanogaster/fisiologia , Vida Livre de Germes , Interações entre Hospedeiro e Microrganismos , Simbiose
18.
Aging (Albany NY) ; 11(21): 9369-9387, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672931

RESUMO

Many studies have indicated that Korean red ginseng (KRG) has anti-inflammatory and anti-oxidative effects, thereby inducing many health benefits in humans. Studies into the longevity effects of KRG are limited and have provided contradictory results, and the molecular mechanism of lifespan extension by KRG is not elucidated yet. Herein, the longevity effect of KRG was investigated in Drosophila melanogaster by feeding KRG extracts, and the molecular mechanism of lifespan extension was elucidated by using longevity-related mutant flies. KRG extended the lifespan of Drosophila when administrated at 10 and 25 µg/mL, and the longevity benefit of KRG was not due to reduced feeding, reproduction, and/or climbing ability in fruit flies, indicating that the longevity benefit of KRG is a direct effect of KRG, not of a secondary artifact. Diet supplementation with KRG increased the lifespan of flies on a full-fed diet but not of those on a restricted diet, and the longevity effect of KRG was diminished by the mutation of dSir2, a deacetylase known to mediate the benefits of dietary restriction. Similarly, the longevity effect of KRG was mediated by the reduction of insulin/IGF-1 signaling. In conclusion, KRG extends the lifespan of Drosophila through Sir2 and insulin/IGF-1 signaling and has potential as an anti-aging dietary-restriction mimetic and prolongevity supplement.


Assuntos
Proteínas de Drosophila/metabolismo , Histona Desacetilases/metabolismo , Insulina/metabolismo , Longevidade/efeitos dos fármacos , Panax , Preparações de Plantas/uso terapêutico , Sirtuínas/metabolismo , Animais , Restrição Calórica , Drosophila melanogaster , Avaliação Pré-Clínica de Medicamentos , Feminino , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fitoterapia , Preparações de Plantas/farmacologia , Estresse Fisiológico/efeitos dos fármacos
19.
Allergy Asthma Immunol Res ; 11(4): 572-582, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31172725

RESUMO

PURPOSE: Children with sensitization to aeroallergens have decreased lung function and nasal patency. Our purpose was to determine the association of sensitization to different aeroallergens with airway function and nasal patency. METHODS: Four hundred and eighty-six randomly selected 11 year-old children who lived in Seongnam City were examined. Serum specific immunoglobulin E (IgE) levels against 6 common allergens (Dermatophagoidesfarinae, birch, cat, dog, Japanese hop and Alternaria), impulse oscillometry (IOS) results for the evaluation of airway dysfunction, and acoustic rhinometry for the determination of nasal airway patency were obtained. RESULTS: IOS indicated that children sensitized to Alternaria (n = 38, 7.8%) and dog dander (n = 69, 14.2%) had decreased lung function, based on resistance at 10 Hz (Rrs10; aß = 0.0072; 95% CI, 0.017, 0.127; P = 0.010) and 1 Hz (Rrs1; aß = 0.038; 95% CI, 0.001, 0.074; P = 0.042). Children sensitized to D. farinae (n = 281, 57.8%) had decreased post-decongestant nasal volume at 0 to 5 cm (aß = -0.605; 95% CI, -1.005, -0.205; P = 0.003), but normal IOS results at all measured frequencies (P > 0.05). Increased serum eosinophil level was associated with Rrs1 (P = 0.007) and Rrs2 (P = 0.018) and post-decongestant nasal volume at 0 to 5 cm (aß = -0.885; 95% CI, -1.331, -0.439; P < 0.001). CONCLUSIONS: Sensitivity to specific aeroallergens, serum eosinophil count and total IgE level had different associations with upper and lower airway dysfunction in urban children.

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